Inhibition of glycosphingolipid biosynthesis does not impair growth or morphogenesis of the postimplantation mouse embryo.
Whole embryo culture (WEC) of organogenesis-stage mouse embryos was adapted for glycosphingolipid (GSL) metabolic studies to evaluate the hypothesis that de novo GSL biosynthesis is a prerequisite for growth and morphogenesis of the early postimplantation embryo. WEC supports the growth and development of postimplantation mouse embryos to stages that are indistinguishable from those achieved in vivo. N-Butyldeoxygalactonojirimycin (NB-DGJ) is an N-alkylated imino sugar that specifically inhibits biosynthesis of all glucosylceramide-based GSLs. NB-DGJ inhibited glucosylceramide and lactosylceramide biosynthesis nearly completely and inhibited ganglioside biosynthesis approximately 90% in both the embryo and visceral yolk sac. NB-DGJ also significantly reduced total ganglioside content in both the embryo and visceral yolk sac as estimated by the cholera toxin immunooverlay technique. A shift in expression from the structurally simple to the structurally complex gangliosides was also observed in NB-DGJ-treated embryos and yolk sacs. Despite causing major changes in GSL biosynthesis and composition, NB-DGJ had no effect on embryo viability, growth, or morphology. The findings suggest that de novo GSL biosynthesis may not be a prerequisite for the growth and morphogenesis of the organogenesis-stage mouse embryo.
Brigande
J V
JV
Department of Biology, Boston College, Chestnut Hill, Massachusetts 02167, USA.
Platt
F M
FM
Seyfried
T N
TN
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002455:Cell Division; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D047108:Embryonic Development; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005699:Galactosylceramides / Q000096:biosynthesis; D005732:Gangliosides / Q000378:metabolism; D006028:Glycosphingolipids / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051379:Mice; D008809:Mice, Inbred C3H; D009024:Morphogenesis; D011247:Pregnancy; D015017:Yolk Sac / Q000187:drug effects / Q000502:physiology
D005699:Galactosylceramides; D005732:Gangliosides; D006028:Glycosphingolipids; D017485:1-Deoxynojirimycin; C090092:migalastat